Integrin-Linked Kinase Controls Choroidal Neovascularization by Recruitment of Endothelial Progenitor Cells

Xiao-sheng, Yang; Duan, Chunguang; Zhang, Jian; Qu, Xiao-jie; Wang, Yusheng

doi:10.1167/iovs.17-22931

Cited by 6 publications

(4 citation statements)

References 22 publications

(32 reference statements)

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“…Disturbances in the balance of secretory proangiogenesis and antiangiogenesis factors trigger an angiogenic switch that fuels DR progression. In the present study, CM from the hypoxia group increased the microvascular density in the Matrigel plug, which is consistent with previous conclusions (Zhu et al, 2016 (Yang, Duan, Zhang, Qu, & Wang, 2018;Yang et al, 2009). In addition, HIF-1α has been demonstrated to bind to hypoxia response elements within the Sp1 promoter to stimulate Sp1 gene transcription activity (Higashimura et al, 2011;Woo et al, 2012).…”

Section: Discussionsupporting

confidence: 93%

“…One possible explanation for this may be that HIF-1α mediates this regulatory relationship. HIF-1α was originally identified as an oxygen-responsive activator and is upregulated in various cell lines, including ARPE-19 cells, under hypoxia (Yang, Duan, Zhang, Qu, & Wang, 2018;Yang et al, 2009). In addition, HIF-1α has been demonstrated to bind to hypoxia response elements within the Sp1 promoter to stimulate Sp1 gene transcription activity (Higashimura et al, 2011;Woo et al, 2012).…”

Section: Ing4 Regulates the Expression Of Several Proangiogenic Facto...mentioning

confidence: 99%

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Inhibitor of growth 4 affects hypoxia‐induced migration and angiogenesis regulation in retinal pigment epithelial cells

Yang

Gong

et al. 2019

Journal Cellular Physiology

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Inhibitor of growth 4 (ING4), a potential tumor suppressor, is implicated in cell migration and angiogenesis. However, its effects on diabetic retinopathy (DR) have not been elucidated. In this study, we aimed to evaluate ING4 expression in normal and diabetic rats and clarify its effects on hypoxia‐induced dysfunction in human retinal pigment epithelial (ARPE‐19) cells. A Type 1 diabetic model was generated by injecting rats intraperitoneally with streptozotocin and then killed them 4, 8, or 12 weeks later. ING4 expression in retinal tissue was detected using western blot analysis, reverse transcription quantitative real‐time polymerase chain reaction (RT‐qPCR), and immunohistochemistry assays. After transfection with an ING4 overexpression lentiviral vector or small interfering RNA (siRNA), ARPE‐19 migration under hypoxia was tested using wound healing and transwell assays. The angiogenic effect of conditioned medium (CM) from ARPE‐19 cells was examined by assessing human retinal endothelial cell (HREC) capillary tube formation. Additionally, western blot analysis and RT‐qPCR were performed to investigate the signaling pathways in which ING4, specificity protein 1 (Sp1), matrix metalloproteinase 2 (MMP‐2), MMP‐9, and vascular endothelial growth factor A (VEGF‐A) were involved. Here, we found that ING4 expression was significantly reduced in the diabetic rats’ retinal tissue. Silencing ING4 aggravated hypoxia‐induced ARPE‐19 cell migration. CM collected from ING4 siRNA‐transfected ARPE‐19 cells under hypoxia promoted HREC angiogenesis. These effects were reversed by ING4 overexpression. Furthermore, ING4 suppressed MMP‐2, MMP‐9, and VEGF‐A expression in an Sp1‐dependent manner in hypoxia‐conditioned ARPE‐19 cells. Overall, our results provide valuable mechanistic insights into the protective effects of ING4 on hypoxia‐induced migration and angiogenesis regulation in ARPE‐19 cells. Restoring ING4 may be a novel strategy for treating DR.

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Section: Discussionsupporting

confidence: 93%

Section: Ing4 Regulates the Expression Of Several Proangiogenic Facto...mentioning

confidence: 99%

Inhibitor of growth 4 affects hypoxia‐induced migration and angiogenesis regulation in retinal pigment epithelial cells

Yang

Gong

et al. 2019

Journal Cellular Physiology

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“…The beneficial effects of these factors on IVM have been demonstrated in several species, such as human [37,38], cow [39], horse [40], pig [41], and mouse [38]. In the present study, it was demonstrated that EPC can secrete various paracrine factors, including bFGF, VEGF, IGF-1, and IL-10, into the extracellular environment, which is consistent with previous findings [42][43][44]. Subsequently, the factors derived from EPC-CM effectively activate the mRNA transcript levels of the receptors (FGFR2 and IGF1R) on COCs during IVM.…”

Section: Discussionsupporting

confidence: 92%

Effects of Human Endothelial Progenitor Cell and Its Conditioned Medium on Oocyte Development and Subsequent Embryo Development

Lee

2020

IJMS

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Human endothelial progenitor cells (EPCs) secrete numerous growth factors, and they have been applied to regenerative medicine for their roles in angiogenesis as well as neovascularization. Angiogenesis is one of the essential factors for the maturation of ovarian follicles; however, the physiological function of EPCs or their derivatives on in vitro culture systems has not been fully understood. The aim of this study was to evaluate the effectiveness of EPCs and their conditioned medium (EPC-CM) on oocyte development and subsequent embryo development. In the results, the oocyte development and subsequent embryo development were significantly improved in EPCs and the EPC-CM group. In addition, markedly increased levels of growth factors/cytokines, such as basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), insulin growth factor-1 (IGF-1), interleukin-10 (IL-10), and epidermal growth factor (EGF), were observed in medium from the EPC-CM group. Additionally, EPC-CM after in vitro maturation (IVM) had significantly decreased reactive oxygen species (ROS) levels compared to those of other groups. Transcriptional levels of growth factor receptor-related genes (FGFR2, IGF1R) and anti-apoptotic-related gene (BCL2) were significantly upregulated in cumulus cells/oocytes from the EPC-CM group compared with those from the control. Furthermore, the expression levels of cumulus expansion-related genes (PTGS2, TNFAIP6, HAS2) and oocyte-maturation-related factors (GDF9, BMP15) were significantly enhanced in the EPC-CM group. Consequently, the present study provides the first evidence that EPC-CM contains several essential growth factors for oocyte development by regulating genes involved in oocyte maturation.

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“…Integrinlinked kinase (ILK) plays multifaceted roles in cellular functions such as cell migration, differentiation, survival, and division and importantly has been highlighted as a key regulator of longevity and of cellular senescence induced by extracellular stressors (Olmos et al, 2017). ILK is also found to be involved in choroidal neovascularization via recruitment of endothelial progenitor cells (Yang et al, 2018), which may be of interest as horseshoe crab is utilised for studies on visual physiology (Hartline et al, 1956;Barlow, 1983;Watson et al, 2008;Battelle, 2016;Battelle et al, 2016).…”

Section: Limulusmentioning

confidence: 99%

Post-translational protein deimination signatures and extracellular vesicles (EVs) in the Atlantic horseshoe crab (Limulus polyphemus)

Bowden

Kraev

Lange

2020

Developmental & Comparative Immunology

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The horseshoe crab is a living fossil and a species of marine arthropod with unusual immune system properties which are also exploited commercially. Given its ancient status dating to the Ordovician period (450 million years ago), its standing in phylogeny and unusual immunological characteristics, the horseshoe crab may hold valuable information for comparative immunology studies.Peptidylarginine deiminases (PADs) are calcium dependent enzymes that are phylogenetically conserved and cause protein deimination via conversion of arginine to citrulline. This posttranslational modification can lead to structural and functional protein changes contributing to protein moonlighting in health and disease. PAD-mediated regulation of extracellular vesicle (EV) release, a critical component of cellular communication, has furthermore been identified to be a phylogenetically conserved mechanism. PADs, protein deimination and EVs have hitherto not been studied in the horseshoe crab and were assessed in the current study. Horseshoe crab haemolymph serum-EVs were found to be a poly-dispersed population in the 20-400 nm size range, with the majority of EVs falling within 40-123 nm. Key immune proteins were identified to be posttranslationally deiminated in horseshoe crab haemolymph serum, providing insights into protein moonlighting function of Limulus and phylogenetically conserved immune proteins. KEGG (Kyoto encyclopaedia of genes and genomes) and GO (gene ontology) enrichment analysis of deiminated proteins identified in Limulus revealed KEGG pathways relating to complement and coagulation pathways, Staphylococcus aureus infection, glycolysis/gluconeogenesis and carbon metabolism, while GO pathways of biological and molecular pathways related to a range of immune and metabolic functions, as well as developmental processes. The characterisation of EVs, and posttranslational deimination signatures, revealed here in horseshoe crab, contributes to current understanding of protein moonlighting functions and EV-mediated communication in this ancient arthropod and throughout phylogeny.

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Integrin-Linked Kinase Controls Choroidal Neovascularization by Recruitment of Endothelial Progenitor Cells

Abstract: We demonstrate that ILK controls the development of CNV by regulating the recruitment of EPC to CNV lesions, possibly through ILK-dependent expression of SDF-1 and VEGF in RPE.

Cited by 6 publications

References 22 publications

Inhibitor of growth 4 affects hypoxia‐induced migration and angiogenesis regulation in retinal pigment epithelial cells

Inhibitor of growth 4 affects hypoxia‐induced migration and angiogenesis regulation in retinal pigment epithelial cells

Effects of Human Endothelial Progenitor Cell and Its Conditioned Medium on Oocyte Development and Subsequent Embryo Development

Post-translational protein deimination signatures and extracellular vesicles (EVs) in the Atlantic horseshoe crab (Limulus polyphemus)

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